DOCK 6.6 This is a release of the version applied in references [1], [2] and [3]. NEW IN DOCK 6.6 ###New Scoring Functions### Two new scoring functions were added: Grid-based footprint scoring function [3] and SASA-based scoring function [2]. ###Orienting Improvements### Orienting code changes and bug fixes. (a) Printing orienting statistics when verbose flag is turned on. (b) Bugfix: Ligand growth no longer fails if the last orient is outside the grid. (c) Bugfix: Orienting code does not seg fault if ligand atoms and spheres are identical. ###Hungarian RMSD### A symmetry corrected RMSD (Hungarian matching) calculation method was added to help evaluate pose reproduction as discussed in reference [1]. ###Miscellaneous### gfortran is now the default Fortran compiler. It comes with any not very old GNU compiler installation. If g77 is desired then hand edit install/config.h to use it. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ DEPRECATED FEATURES 1. For a variety of reasons still under active development, amber_score cannot effectively be used as a secondary_score. This function was temporarily deprecated in 6.1, and using input parameter amber_score_secondary causes program termination. The recommended protocol is to perform two DOCK runs with the second run specifying amber_score as the primary_score. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ BUG FIXES Some bug reports have not yet been processed, but several important bugs have been fixed since the last release. For DOCK: As discussed above, two bugs that related to the orienting code were fixed. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ INPUT PARAMETER CHANGES AND THEIR DEFAULT VALUES Added: For SASA descriptor Score: SASA_descriptor_score_primary [no] (yes no): SASA_descriptor_score_secondary [no] (yes no): SASA_descriptor_score_rec_filename [receptor.mol2] (): For MultiGrid Score: multigrid_score_primary [no] (yes no): multigrid_score_secondary [no] (yes no): multigrid_score_rep_rad_scale [1] (): multigrid_score_vdw_scale [1] (): multigrid_score_es_scale [1] (): multigrid_score_number_of_grids [20] (): multigrid_score_grid_prefix0 [multigrid0] (): multigrid_score_grid_prefix1 [multigrid1] (): multigrid_score_grid_prefix2 [multigrid2] (): . . . multigrid_score_grid_prefix19 [multigrid19] (): multigrid_score_fp_ref_mol [no] (yes no): multigrid_score_fp_ref_text [no] (yes no): Removed: ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ FILE FORMAT CHANGES For DOCK: New scoring function SASA descriptor score has the following output: SA_Descriptor Score: 0.00 %_lig_exposed: 0.00 %_phobic_lig_buried: 100.00 %_phobic_rec_buried: 1.75 %_lig_phobic_buried/tot_buried: 86.23 %_rec_phobic_buried/tot_buried: 90.69 rec_sasa_tot: 12383.63 rec_sasa_phobic: 9737.08 rec_sasa_philic: 2646.54 rec_sasa_other: 0.00 lig_sasa_tot: 540.48 lig_sasa_phobic: 466.06 lig_sasa_philic: 74.42 lig_sasa_other: 0.00 com_sasa_tot: 12195.38 com_sasa_phobic: 9566.36 com_sasa_philic: 2629.01 com_sasa_other: 0.00 com_sasa_tot_lig: 0.00 com_sasa_phobic_lig: 0.00 com_sasa_philic_lig: 0.00 com_sasa_other_lig: 0.00 com_sasa_tot_rec: 12195.38 com_sasa_phobic_rec: 9566.36 com_sasa_philiic_rec: 2629.01 com_sasa_other_rec: 0.00 The new scoring function MultiGrid Score has the following output: MultiGrid Score: -42.921688 MultiGrid_vdw: -39.637810 MultiGrid_es: -4.158845 vdwcor: 0.936048 escor: 0.778960 vdweuc: 4.136627 eseuc: 1.506654 vdwnorm: 0.268077 esnorm: 0.606887 array length = 15 printing grid arrays: name: VDW, ES grid0: -4.498144, -0.137712 grid1: -4.462515, -0.161382 grid2: -1.520630, -0.052917 grid3: -0.950182, 0.414807 grid4: -0.878499, -0.022798 grid5: 1.841859, -0.652629 grid6: -4.153936, -0.470118 grid7: -1.597689, -1.876638 grid8: -1.662990, -0.481926 grid9: -1.414446, -0.001891 grid10: -2.581383, -0.079574 grid11: -1.394126, 0.009340 grid12: -3.464417, -0.007966 grid13: -0.686095, 0.096706 grid14: -12.214619, -0.734148 The label for RMSD's in output files has changed from '########## HA_RMSD' to three types of RMSD's: HA_RMSDs (standard RMSD), HA_RMSDh (symmetry-corrected RMSD) and HA_RMSDm (min RMSD). The following is an example: ########## HA_RMSDs: 1.4729 ########## HA_RMSDh: 1.4729 ########## HA_RMSDm: 0.8748 In addition, new verbose statistics were added. These are controlled by the verbose flag. The following is an example: ----------------------------------- VERBOSE ORIENTING STATS : Orienting 23 anchor heavy atom centers Sphere Center Matching Parameters: tolerance: 0.25; dist_min: 2; min_nodes: 3; max_nodes: 10 Num of cliques generated: 4315 Residual Info: min residual: 0.0197 median residual: 0.1990 max residual: 0.2500 mean residual: 0.1877 std residual: 0.0474 Node Sizes: min nodes: 3 max nodes: 4 mean nodes: 3.0023 ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ REFERENCES 1. Brozell, S. R.; Mukherjee, S.; Balius, T. E.; Roe, D. R.; Case, D. A.; Rizzo, R. C. Evaluation of DOCK 6 as a Pose Generation and Database Enrichment Tool,J. Comput-Aided Mol. Des., 2012, 26, 749-773 dx.doi.org/10.1007/s10822-012-9565-y. 2. Holden, P. M.; Rizzo, R. C. Pose Selection and Stability of HIVgp41 Inhibitors using Molecular Footprints, J. Chem. Theory Comput., 2012, Submitted. 3. Balius, T. E.; Allen, W. J.; Mukherjee, S.; Rizzo, R. C. Grid-Based Molecular Footprint Comparison Method for Docking and De Novo Design: Application to HIVgp41, J. Comp. Chem., 2012, Submitted.